Coccidioidomycosis is a fungus disease associated with a cellular immune defect. Characteristically, patients with chronic or progressive disease have depressed skin tests and in vitro lymphocyte responses to Coccidioides immitis antigens. The immune defect is, in most patients, specific for C. immitis. However, some, more commonly those with disseminated disease, show anergy to antigens unrelated to C. immitis. A second characteristic feature of this disease is a B-cell hyperreactivity manifested as a polyclonal gammopathy on serum electrophoresis. In preliminary studies directed towards more fully characterizing B cell hyperreactivity in coccidioidomycosis, we found elevated IgE levels in approximately 59% of patients with active pulmonary and/or disseminated disease and 33% of patients with inactive disease. This finding coupled with the increased frequency of reports that serum IgE antibodies are elevated in other diseases associated with a cellular immune defect warrants further study into the role of IgE in coccidioidomycosis. The proposed research will establish the frequency of increased serum levels of IgE in patients with coccidioidomycosis; assess the specificity of the IgE antibodies, determine the temporal relationship between serum IgE and the clinical status of patients with this disease, and evaluate the effect of IgE on in vitro cell-mediated immune responses.